A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor.
Mice lacking the epidermal growth factor receptor (EGFR) exhibit strain-dependent phenotypes ranging from placental to postnatal skin, lung and brain defects. After birth, all mutant mice develop a progressive neurodegeneration in the frontal cortex, olfactory bulb and thalamus, characterized by massive apoptosis and upregulation of c-fos. These defects occur in a strain-independent manner, since neither rescue of the placental phenotype by aggregation of diploid 129/Sv EGFR mutant and tetraploid wild-type embryos, nor promotion of lung maturation by transplacental dexamethasone administration alters the course of neurodegeneration. VEGF is not induced during the degenerative process, excluding hypoxia and ischemia as causes of cell death. A migratory disorder is detected in the hippocampus with nests of ectopic neurons, which are also apoptotic. Cerebral cortices from EGFR mutants contain lower numbers of GFAP positive astrocytes, which display reduced proliferation in vitro. Since EGFR is expressed in the affected cell-types, these results define a specific function for EGFR in the proliferation and/or differentiation of astrocytes and in the survival of postmitotic neurons.
Sibilia
M
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Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Steinbach
J P
JP
Stingl
L
L
Aguzzi
A
A
Wagner
E F
EF
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002490:Central Nervous System / Q000503:physiopathology; D066246:ErbB Receptors / Q000172:deficiency*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D000860:Hypoxia; D008168:Lung / Q000098:blood supply; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009389:Neovascularization, Pathologic; D009410:Nerve Degeneration / Q000235:genetics*; D010920:Placenta / Q000098:blood supply; D013045:Species Specificity; D013788:Thalamus / Q000473:pathology
D066246:ErbB Receptors